The movie begins in a alternate universe where Lex Luthor and a heroic analogue to The Joker named The Jester are securing a piece of technology at a secret lair of the Crime Syndicate, an evil version of the Justice League. After securing the unknown device, Luthor and The Jester attempt to escape, only to have the Jester sacrifice himself while killing J'edd J'arkus (a Martian Manhunter analogue), and Angelique (a Hawkgirl analogue). Lex Luthor is then confronted by the Syndicate, only to escape to the Earth of the heroic Justice League.

Once there, he ends up having a run-in with the police. The Justice League is called in and confronts the heroic Lex Luthor (who had to be strip-searched). Upon Superman's x-ray vision confirming that this Lex Luthor is from another Earth and that the Lex Luthor that he knows is still at Stryker's Island, the Justice League agree to hear Lex out. After telling the Justice League his story on the Watchtower, Lex recruits the League to help save his Earth from the Syndicate, who have taken control of all crime on Earth and systematically eliminated Luthor's League one by one. After a passionate debate, the Justice League decides to help Luthor despite their mistrust and misgivings. Batman stays behind arguing the League is spread too thin to solve the problems of their own world, let alone Luthor's. Luthor transports the remaining members of the League to his universe, while Batman stays behind to finish rebuilding the Watchtower.

The League encounters a parallel world where Slade Wilson is President of the United States. The world is being extorted by the Crime Syndicate, and the only thing holding the Syndicate in check is the threat of nuclear retaliation by the nations of the world against their base on the Moon.

Owlman is building a weapon, the Quantum Eigenstate Device or QED, that can presumably destroy entire cities, which the Syndicate intends to use as the equalizer to the nuclear threat of the world's governments. When pressed by his romantic interest, Superwoman, Owlman admits the weapon can destroy entire worlds. Operating under the theory that there are many parallel Earths, and that each one develops from our choices, he begins seeking Earth-Prime, the first Earth. Owlman, a nihilist, believes that the only choice not invalidated by the creation of a counter-posed universe is to end the multiverse itself. Superwoman notes that even as a "murdering psychopath", she thinks Owlman is much crazier than she is.

He is stopped by Batman at the last moment, who sends him to an uninhabited world that is harmlessly destroyed. Owlman has had the opportunity to disarm the QED before it explodes, but does nothing, saying "it doesn't matter", placing a Q.E.D. on his nihilist philosophy.